Role of the acidic receptosome in the uptake and retention of 67Ga by human leukemic HL60 cells.
The uptake of 67Ga by HL60 cells requires binding of 67Ga-transferrin (Tf) to cell surface Tf receptors. To further examine this process, we have studied early events in the cellular uptake of 67GaTf. Cell surface-bound 67GaTf and 59FeTf displayed similar kinetics during the first 10 min of uptake. Thereafter, approximately 10% of intracellular 67Ga was released by cells while 59Fe internalization continued to increase with time. In pulse-chase studies of 125I-Tf-67Ga uptake, internalized 125I-Tf, but not 67Ga, was chased out of cells by nonradioactive Tf-Ga. Exposure of cells to monensin, a carboxylic ionophore, during initial uptake decreased the internalization of both 125I-Tf and 67Ga. Exposure to monensin at a later time, after cells had incorporated 125I-Tf-67Ga or 59FeTf, caused an increase in the release of 67Ga and 59Fe with a decrease in the release of 125I-Tf. Ammonium chloride inhibited the internalization of both 67Ga and 59Fe. 67GaTf uptake by HL60 cells involves initial internalization into an acidic receptosome. This is followed by dissociation of 67Ga and Tf and subsequent trafficking of each to separate intracellular compartments. Disruption of this process by monensin results in the release of 67Ga from cells.
Chitambar
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CR
Department of Medicine, Medical College of Wisconsin, Milwaukee 53226.
Zivkovic-Gilgenbach
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D005710:Gallium Radioisotopes / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008985:Monensin / Q000494:pharmacology*; D011990:Receptors, Transferrin / Q000378:metabolism*; D013997:Time Factors; D014168:Transferrin / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000378:metabolism
D005710:Gallium Radioisotopes; D011990:Receptors, Transferrin; D014168:Transferrin; D008985:Monensin; D007501:Iron